The overall objective of the proposed studies is to define how opiate narcotics regulate RNA and protein synthesis in the brain to achieve tolerance and physical dependence. The quantitative, qualitative, and temporal changes produced by morphine in regulatory processes at the level of RNA and protein synthesis and/or degradation in various brain regions will be analyzed and related to the development of tolerance and physical dependence. The proteins induced by morphine in various brain regions will be isolated, identified, purified and characterized. Groups of rats (normal and morphine tolerant) will be pulse-labelled with RNA and protein precursors. Brains will be dissected into morphologically distinct regions, and messenger RNA, ribosomal RNA, free and bound polysomes, nascent polypeptides and proteins will be isolated and analyzed. Techniques of liquid scintillation spectrometry, chromatography, electrophoresis and centrifugation will be employed to fractionate and analyze populations of macromolecules. These studies will provide data on the changes induced by morphine in RNA and protein metabolism and how they relate to the development of tolerance to and physical dependence on opiate narcotics.